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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 415 records · Page 23Linked to original sources
PubMed1988

Phase I study of recombinant gamma-interferon (rIFN-gamma).

A Phase I study of recombinant gamma-interferon was conducted in 35 patients with advanced malignancy. The schedule was twice weekly administered intravenously. Patients were assigned to six dose levels. The major toxicities were flu-like symptoms and were unrelated to dose. Other adverse reactions, such as myelosuppression, were dose dependent. The addition of a nonsteroidal anti-inflammatory agent did not ameliorate the symptoms at the highest dose level. Antitumor effects occurred in patients with gastric, duodenal, and breast carcinoma.

Drug Evaluation↗
PubMed1988

Phase I study of recombinant methionyl human consensus interferon (r-metHuIFN-Con1).

Consensus interferon (r-metHuIFN-Con1) is the product of a gene constructed to code for the most frequent amino acid residues known to occur in subspecies of alpha interferons. Twenty-one patients with advanced malignancy entered this phase I trial with dosing levels of 3, 7.5, 15, 30, and 45 mcg/m2/day given intramuscularly on days 1-5 and 8-10 of each 28-day cycle. The initial dose was randomly given by intravenous, intramuscular, or subcutaneous injection to facilitate pharmacokinetic studies. Vomiting and diarrhea were dose-limiting at 45 mcg/m2/day, preventing completion of therapy. Malaise, flu-like symptoms, nausea, and headache were frequent but tolerable at a dose of 30 mcg/m2/day. Patients were able to escalate to 45 mg/m2/day, suggesting tachyphlaxis to these toxicities. The initial distribution phase (T1/2 alpha) was 4.9-9.0 minutes with a T1/2 beta of 34-415 minutes in three patients for whom sequential values could be determined. r-MetHuIFN-Con1 was absorbed after both subcutaneous and intramuscular administration. 2'5'-Synthetase levels increased following treatment, although no consistent pattern was noted. One partial response was seen in a patient with gastrointestinal carcinoma. The recommended phase II starting dose of r-metHuIFN-Con1 is 30 mg/m2/day using this schedule by any of these routes of administration.

Adolescent↗
PubMed1987

Enzymatic transformation of mercapturic acids derived from halogenated alkenes to reactive and mutagenic intermediates.

The metabolism of the mercapturic acids S-pentachlorobutadienyl-N-acetylcysteine (N-Ac-PCBC), S-trichlorovinyl-N-acetylcysteine (N-Ac-TCVC) and S-dichlorovinyl-N-acetylcysteine (N-Ac-DCVC) by subcellular fractions from male rat liver and kidney homogenates was studied. As a model compound, N-Ac-PCBC, 14C labelled, was synthesised. It was intensively metabolised by cytosolic but not by microsomal enzymes from rat liver and kidney. The major metabolite identified by GC/MS was pentachlorobutadienylcysteine, the amount produced being highest in kidney cytosol. Metabolic conversion of 14C-N-Ac-PCBC by kidney and liver cytosol resulted in covalent binding of radioactivity to protein, binding was strongly inhibited by the beta-lyase inhibitor aminooxyacetic acid (AOAA). N-Ac-TCVC and N-Ac-DCVC were also transformed by cytosolic enzymes to the corresponding cysteine conjugates (trichlorovinylcysteine and dichlorovinylcysteine). The three mercapturic acids tested were strong mutagens in the Ames-test after addition of rat kidney cytosol. In the absence of cytosol, N-Ac-TCVC and N-Ac-DCVC were weakly but definitely mutagenic, whereas N-Ac-PCBC was not. In contrast to N-Ac-PCBC, the "direct" mutagens N-Ac-TCVC and N-Ac-DCVC were both transformed to pyruvate by bacterial (S. typhimurium TA100) homogenate 100,000 g supernatants. It is concluded that mercapturic acids are deacetylated to the corresponding cysteine conjugates by cytosolic (N-Ac-PCBC, N-Ac-TCVC and N-Ac-DCVC) and bacterial enzymes (N-Ac-TCVC and N-Ac-DCVC) and further cleaved to reactive and mutagenic intermediates by mammalian and/or bacterial beta-lyase. The observed activation mechanisms for the mercapturic acids, whose formation from hexachlorobutadiene, tetrachloroethylene and trichloroethylene has been proven, might contribute to the nephrotoxicity and nephrocarcinogenicity of the parent alkenes.

Acetylation↗
PubMed1987

In vitro and in vivo behaviour of rat islets of Langerhans treated with MHC antisera and complement.

The in vitro and in vivo behaviour of rat islets of Langerhans pretreated with polyclonal MHC antisera and complement was investigated. Complement-dependent cytotoxicity against rat islets was mediated by the antisera which were either directed against all MHC products ("a anti-u") or against products of the B-region of rat MHC ("Ba anti-Bu"). There were only minor alterations in glucose-stimulated insulin secretion and in 3H-leucine incorporation into islet proteins and into (pro)insulin in the pretreated islets. The syngeneic transplantation of "Ba anti-Bu"-treated islets led to a permanent graft survival in all streptozotocin-diabetic rats but after "a anti-u"-pretreatment permanent graft survival was only achieved in 33% of the syngeneic recipients. It is concluded, that in the latter case a complement-dependent cytotoxicity is exerted against the islets which may not allow sufficient in vivo survival. Now it appears necessary to look for effects of pretreatment prior to an allogeneic transplantation.

Animals↗
PubMed1987

Nucleotide sequence of Bacillus subtilis dnaB: a gene essential for DNA replication initiation and membrane attachment.

The complete nucleotide sequence of the Bacillus subtilis dnaB gene and its flanking regions was determined. The dnaB gene is essential for both replication initiation and membrane attachment of the origin region of the chromosome and plasmid pUB110. It has been known that there are two different classes (dnaBI and dnaBII) in the dnaB mutants; dnaBI is essential for both chromosome and pUB110 replication, whereas dnaBII is necessary only for chromosome replication. The nucleotide sequence revealed that dnaBI and dnaBII are two functional domains in the single dnaB gene. The mutation sites of two mutants, belonging to dnaBI and dnaBII, respectively, were also determined as substitutions of amino acids. The putative DnaB protein deduced from nucleotide sequence consists of 472 amino acids (55 kDa) with no cysteine residue. A 55-kDa polypeptide produced in an in vitro transcription-translation system was labeled with [35S]methionine but not with [35S]cysteine. The DnaB protein has a highly hydrophobic sequence of 20 amino acids in its N-terminal region, a possible DNA binding site, and two possible ATP binding sites. The dnaBI domain is between the DNA binding site and one of the ATP binding sites; the dnaBII domain is close to the other ATP binding site. Comparison of the amino acid sequence between the "dnaB protein" and those of other dna genes of Escherichia coli showed no homology, suggesting that the dnaB gene of B. subtilis may be analogous to a hitherto undiscovered gene in E. coli.

Amino Acid Sequence↗
PubMed1987

Fetal distress and the condition of the newborn using cardiotocography and fetal blood analysis during labour.

The efficacy of electronic fetal monitoring combined with fetal blood analysis during labour in identifying fetal distress was investigated in a retrospective study. Operative delivery for fetal distress diagnosed during labour was performed in 9% of 2659 deliveries. All had continuous fetal heart rate monitoring and 22% had a fetal scalp blood analysis. Operative delivery had been performed in 53% of the infants who were acidotic at birth (umbilical artery pH less than 7.20) and in 46% of those with a low modified Apgar score (less than 7). These results show that the use of continuous fetal heart rate monitoring and fetal scalp blood sampling detects fetal distress without resulting in a high rate of operative delivery.

Apgar Score↗
PubMed1987

Comparative study of application techniques for the tcPCO2 measurement in the fetus.

In order to investigate the advantages and shortcomings of two application techniques proposed for the tcPCO2 electrode in the fetus we performed a trial using two electrodes with different modes of fixation synchronously. Comparing the transcutaneously measured values with the values of the fetal blood we found a statistically significant correlation for both techniques (r = 0.83 and 0.80, respectively). The mean values of the tcPCO2 though were significantly higher when the suction fixation was used compared with the glue fixation.

Blood Gas Monitoring, Transcutaneous↗
PubMed1987

Plasma immunoreactive beta-endorphin, ACTH and cortisol concentrations in mothers and their neonates immediately after delivery--their relationship to the duration of labor.

In 29 cases of vaginal delivery with normal outcome and 4 cases of cesarean section, the concentrations of beta-endorphin, ACTH and cortisol were determined in maternal venous and umbilical venous plasma immediately postpartum. According to duration of labor and mode of delivery the cases examined were classified into three groups: Group A (18 cases) = vaginal delivery of less than 10 hours' duration, Group B (11 cases) = vaginal delivery of more than 10 hours' duration of labor, Group C (4 cases) = cesarean section under general anesthesia. With the exception of one, the deliveries took place at term. The 33 neonates were in a very good clinical state 5 minutes after parturition (11 Saling points as median value). For measurement of the hormone concentrations radioimmunoassays were used. In Group a the mean beta-endorphin concentration in maternal plasma amounted to 150.9 +/- 16.3 pg/ml, that in neonatal plasma to 239.2 +/- 23.5 pg/ml (means +/- SEM). In Group B plasma beta-endorphin, both maternal and neonatal, was slightly higher than in Group A: 153.0 +/- 12.0 pg/ml (maternal) and 260.9 +/- 37.1 pg/ml (neonatal). The differences between maternal and neonatal beta-endorphin levels were statistically significant: Group A p less than 0.01, Group B p less than 0.05; chi 2-test. The mean ACTH concentrations in the plasma of the newborn infants were also found to be considerably higher compared with those in the plasma of their mothers: Group A 78.2 +/- 16.5 pg/ml (maternal) and 98.0 +/- 23.3 pg/ml (neonatal); Group B 98.0 +/- 20.1 pg/ml (maternal) and 165.8 +/- 39.6 pg/ml (neonatal).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Glue fixation of the tcPco2 electrode for fetal monitoring.

tcPco2 monitoring on the fetal scalp potentially is a beneficial and additional new tool for the surveillance of the unborn child. During a clinical trial we investigated the tcPco2 monitoring using the glue fixation technique. A modified Severingshaus electrode was applied on a prepared area on the fetal scalp by means of an endoscope. The attempt of application was successful in 224 out of 245 cases, while reapplication was only necessary in 8 cases. The accuracy of the tcPco2 measurement using glue fixation was sufficient at both measuring temperatures (39 degrees C and 44 degrees C). The correlation coefficient comparing the data with the tcPco2 of the fetal blood was 0.74 respectively 0.81. The development of a caput succedaneum leads to higher absolute values of the tcPco2. When a caput succedaneum has developed in the measuring area the mean value of the tcPco2 is significantly higher (62.70 mmHg instead of 55.14 mmHg respectively 68.98 mmHg instead of 65.98 mmHg) at 39 degrees C respectively 44 degrees C. No significant influence of different preparation techniques of the measuring site has been found during this investigation. The glue fixation technique leads to a reliable recording of tcPco2 in the fetus during labor, when the electrode is placed in a central and not compressed position on the lower pole of the fetus. The disadvantage is the necessity of extensive training of the personnel and the large number of instruments, factors that will interfere with a more widespread use in clinical routine.

Adhesives↗
PubMed1987

Clinical experience on tcPco2 during labor.

tcPco2 measurements in the fetus during labor were evaluated by analysing the clinical experience in 224 cases. This additional mode of supervision was performed in combination with continuous cardiotocography (CTG) and intermittent fetal blood sampling (FBA) in cases with suspect, prepathologic or pathologic heart rate patterns. The prechosen measuring temperature was 39 degrees C in 105 and 44 degrees C in 119 cases. The normal range of the tcPco2 was defined by calculating the mean value and two standard deviations in cases without hypoxic complications. The absolute values of the normal range were different according to the measuring temperature, when no correction factor was used. After adjusting the transcutaneous values to the blood gas level by means of the Severinghaus formular no significant differences in the tcPco2 values were notified for the two applied temperatures (39 degrees C and 44 degrees C). There is an obvious rise of tcPco2 with the progress of labor. Comparing the tcPco2 values with the pH values in the fetal blood we found a statistically significant correlation at either temperatures (p less than 0.001). Aiming at an early detection of raising acidity in the fetal blood, an action line of 55 mmHg after correction (80 mmHg at 44 degrees C, 63 mmHg at 39 degrees C) is an adequate basis for clinical intervention as all acidotic (pH less than 7.20) and the majority of preacidotic value (pH 7.20-7.24) can be excluded. One clinical benefit that can be expected by the additional use of tcPco2 is the reduction in the necessity of fetal blood sampling in a number of cases with abnormal heart rate patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Gas Monitoring, Transcutaneous↗
PubMed1987

On the daily variation in the beta-receptor-adenylate cyclase-cAMP-phosphodiesterase system in rat forebrain.

In rat forebrain tissue of single rats beta-adrenoceptor density (Bmax) and affinity (Kd) were determined by saturation isotherms in receptor binding studies with the antagonist ligand (3H)-dihydroalprenolol at 8 different times of day in May. Rats were on a controlled 12L:12D photoperiod. In addition, the cAMP content, the formation of cAMP from ATP by the adenylate cyclase and the hydrolysis of the second messenger by the phosphodiesterase were determined at the same time points. No significant (ANOVA) daily variations were found in the total number of 3H-DHA binding sites (Bmax) nor in the affinity (Kd). In contrast, basal cAMP content as well as basal formation and hydrolysis of cAMP displayed significant rhythms. The peak value in cAMP was at the beginning of light. At that time the daily trough value in cAMP formation was found. Hydrolysis of cAMP by the phosphodiesterase displayed a 12-hr rhythm with trough values occurring at the early light and early dark period. The results demonstrate pronounced rhythmic changes in basal formation, content and hydrolysis of cAMP which are, however, not paralleled by changes in receptor number and/or affinity in the same tissue.

Adenosine Triphosphate↗
PubMed1987

[Paraneoplastic limbic encephalopathy, inappropriate ADH secretion and recurrent subclinical epileptic seizures. Clinical, anatomo-pathological and metabolic correlations by positron emission tomography].

We report a case of limbic encephalopathy clinically characterized by a progressive amnestic syndrome and many EEG seizures mainly localized on the left temporal area. Biological investigations revealed diabetes mellitus and a syndrome of inappropriate antidiuretic hormone secretion (IADH). Haemodynamic and metabolic studies by positron-emission tomography showed an important increase in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen on the left anterior temporal region precisely where the electrical seizures were recorded. Nine months later, severe disorders of memory and a dramatic decrease in CBF and CMRO2 on the same area region were present. At autopsy, a small size oat cell bronchial carcinoma was found with metastases in two small adjacent lymph nodes. Neuropathological examination showed atrophy (neuronal loss, protoplasmic gliosis) in the amygdala; where there was in addition an area of nodular gliosis. The hippocampus and parahippocampal gyrus lesions were severe on the left and moderate on the right side. The authors discuss the nosology of their case in the paraneoplastic syndromes and, with a review of the literature, the role of ADH and cellular hyperactivity in the pathogenesis of specifically localized neuronal alterations.

Amnesia↗
PubMed1987

[Increased concentrations of atrial natriuretic peptide in the plasma and heart atrium of patients with aortic and mitral valve diseases compared to patients with coronary heart disease].

Plasma levels of atrial natriuretic peptide (ANP) and tissue content of the peptide were measured simultaneously in 18 patients with coronary heart disease (group A) and 10 patients with aortic or mitral dysfunction (group B) undergoing open heart surgery. Plasma levels of ANP were significantly higher in patients with valvular heart disease compared to those with coronary heart disease (816 +/- 246 pg/ml versus 232 +/- 58 pg/ml, p less than 0.005). Similarly, tissue levels of ANP in the right atrium of group B doubled that of group A (227 +/- 46 micrograms/g versus 129 +/- 15 micrograms/g, p less than 0.025). Plasma levels and tissue content of ANP were not correlated. However, plasma ANP levels and mean pulmonary artery pressure were positively correlated (r = 0.688, p less than 0.05). Chronic stimulation of ANP secretion leads to a tissue accumulation of natriuretic peptide in heart atrium.

Aged↗
PubMed1987

[Ultrasonic studies of the liver in dogs and cats].

Sonography of the liver is an easy and safe method for the evaluation especially of circumscribed liver lesions. The criteria for diagnosis and some indications are described. The findings of different liver diseases are discussed.

Animals↗
PubMed1987

[The congenital portosystemic shunt in dogs and cats. I].

An overview of the circulation of the liver and of the pathogenesis of hepatic encephalopathy as a result of portal vascular anomalies is given. Clinical signs associated with portal systemic shunts are described on the basis of 16 cases, 14 dogs and 2 cats. These animals ranged in age at the time of presentation from 4 months to 7 years. The predominant abnormality observed were central nervous signs, which differed in severity. 15 animals showed a reduction in liver size. The different techniques of contrast angiography allowing demonstration of a portal systemic shunt are presented along with a discussion of the pros and cons of each. Additionally the significance of making portal venous pressure measurements prior to each angiography is also explained. In most cases mesenteric portography was chosen. Based on their location the anomalies could be categorized as intrahepatic (4 dogs) or extrahepatic (10 dogs, 2 cats). In both groups breeds of various size are represented. The extrahepatic shunts could be further described as portal-caval (n = 5), portal-phrenic (n = 4) and portal-azygos (n = 3). In five of the older animals angiography showed in addition some hepatic perfusion by the portal vein. Laboratory evaluation revealed increased resting blood ammonia concentrations (greater than 200-912 micrograms/100 ml) in all animals. Seven dogs had definitely subnormal BUN concentrations (less than 10 mg%) and ten dogs low total plasmaprotein levels (less than 5.4 g%). Free amino acids (24) were determined in four dogs and a lowered hepatic encephalopathy index (less than 1.64) was found. Medical palliative therapy to control the clinical signs is discussed. The only effective long term therapy is, however, surgery. The shunt vessel is narrowed so that a greater volume of portal blood reaches the liver. Experience gained from the surgical therapy of 14 animals is presented. Ten of these survived well without requiring further therapy at a later time. Finally the etiology, prognosis, and differential diagnosis are summarized.

Animals↗